tbuckley/cabot-search huggingface dataset:
COVID-19 vaccines protect children of all ages
Authors: Justin Z. Amarin, Haya Hayek, Natasha B. Halasa
Journal: Journal of Clinical Investigation (2022)

As of June 30, 2022, there have been 87,298,343 cases of coronavirus disease 2019 reported in the United States, of which approximately 17.4% occurred in children 0-17 years old (1).So far in 2022, individuals 0-19 years old have accounted for 23.6% of cases, a considerable increase, from 14.4%, throughout 2020 (Figure 1).The increasing case burden in children corresponds with differential vaccine access and uptake compared with adults, of whom the vast majority received an mRNA COVID-19 vaccine ref. 1).The first Emergency Use Authorization (EUA) for Pfizer-Bi-oNTech was issued on December 11, 2020, by the FDA, and it was the only available option for individuals 16 years and older (Figure 1 and ref. 2).It was not until May 10, 2021, almost 5 months later, that the FDA expanded the EUA for Pfizer-BioNTech to include adolescents 12-15 years old (Figure 1 and ref. 3).Some 6 months after that, on November 3, 2021, the US FDA amended the EUA to include children 5-11 years old (Figure 1 and refs. 1, 4).More than 1.5 years after the first EUA, on June 17, 2022, the Pfizer-BioNTech and Moderna COVID-19 vaccines were authorized for use in children 6 months and older (Figure 1 and ref. 5).Notably, Moderna had only been authorized for use in adults 18 years and older prior to the most recent EUA amendment (5).Despite the CDC recommendation that everyone 6 months and older get vaccinated against COVID-19, vaccine uptake has been suboptimal in children compared with adults; 63.4% of children 5-11 years old were unvaccinated as of June 30, 2022, as opposed to 30.0% of adolescents 12-17 years old and 10.1% of adults at aged 18 years and older (1).According to a systematic
IFN-α with dasatinib broadens the immune repertoire in patients with chronic-phase chronic myeloid leukemia
Authors: Jani Huuhtanen, Mette Ilander, Bhagwan Yadav, Olli M.J. Dufva, Hanna Lähteenmäki, Tiina Kasanen, Jay Klievink, Ulla Olsson-Strömberg, Jesper Stentoft, Johan Richter, Perttu Koskenvesa, Martin Höglund, Stina Söderlund, Arta Dreimane, Kimmo Porkka, Tobias Gedde-Dahl, Björn T. Gjertsen, Leif Stenke, Kristina Myhr-Eriksson, Berit Markevärn, Anna Lübking, Andreja Dimitrijevic, Lene Udby, Ole Weis Bjerrum, Henrik Hjorth-Hansen, Satu Mustjoki
Journal: Journal of Clinical Investigation (2022)

In chronic myeloid leukemia (CML), combination therapies with tyrosine kinase inhibitors (TKIs) aim to improve the achievement of deep molecular remission that would allow therapy discontinuation. IFN-α is one promising candidate, as it has long-lasting effects on both malignant and immune cells. In connection with a multicenter clinical trial combining dasatinib with IFN-α in 40 patients with chronic-phase CML (NordCML007, NCT01725204), we performed immune monitoring with single-cell RNA and T cell receptor (TCR) sequencing (n = 4, 12 samples), bulk TCRβ sequencing (n = 13, 26 samples), flow cytometry (n = 40, 106 samples), cytokine analyses (n = 17, 80 samples), and ex vivo functional studies (n = 39, 80 samples). Dasatinib drove the immune repertoire toward terminally differentiated NK and CD8+ T cells with dampened functional capabilities. Patients with dasatinib-associated pleural effusions had increased numbers of CD8+ recently activated effector memory T (Temra) cells. In vitro, dasatinib prevented CD3-induced cell death by blocking TCR signaling. The addition of IFN-α reversed the terminally differentiated phenotypes and increased the number of costimulatory intercellular interactions and the number of unique putative epitope-specific TCR clusters. In vitro IFN-α had costimulatory effects on TCR signaling. Our work supports the combination of IFN-α with TKI therapy, as IFN-α broadens the immune repertoire and restores immunological function.
This Month's Highlights
Journal: Journal of the American Society of Nephrology (2022)

Corresponding Article Sources of Variation in the Carbon Footprint of Hemodialysis Treatment Sehgal, Ashwini R.; Slutzman, Jonathan E.; Huml, Anne M. Journal of the American Society of Nephrology. 33(9):1790-1795, September 2022. Assessing the Carbon Footprint of Hemodialysis: A First Step Toward Environmentally Sustainable Kidney Care Barraclough, Katherine A.; McAlister, Scott Journal of the American Society of Nephrology. 33(9):1635-1637, September 2022. Hurricanes and Mortality among Patients Receiving Dialysis Blum, Matthew F.; Feng, Yijing; Anderson, G. Brooke; Segev, Dorry L.; McAdams-DeMarco, Mara; Grams, Morgan E. Journal of the American Society of Nephrology. 33(9):1757-1766, September 2022. Complement C3a and C3a Receptor Activation Mediates Podocyte Injuries in the Mechanism of Primary Membranous Nephropathy Gao, Shuang; Cui, Zhao; Zhao, Ming-hui Journal of the American Society of Nephrology. 33(9):1742-1756, September 2022. Complement is Complimentary in Membranous Nephropathy Kettritz, Ralph; Schreiber, Adrian Journal of the American Society of Nephrology. 33(9):1631-1633, September 2022. Effects of Short-Term Potassium Chloride Supplementation in Patients with CKD Gritter, Martin; Wouda, Rosa D.; Yeung, Stanley M.H.; Wieërs, Michiel L.A.; Geurts, Frank; de Ridder, Maria A.J.; Ramakers, Christian R.B.; Vogt, Liffert; de Borst, Martin H.; Rotmans, Joris I.; Hoorn, Ewout J.; on behalf of K+onsortium Journal of the American Society of Nephrology. 33(9):1779-1789, September 2022. Searching for the Risk-Benefit Profile of Higher Potassium Intake in CKD: Primum Non Nocere Guedes, Murilo; Pecoits-Filho, Roberto Journal of the American Society of Nephrology. 33(9):1633-1635, September 2022. The Highs and Lows of Potassium Intake in CKD—Does One Size Fit All? Terker, Andrew S.; Saritas, Turgay; McDonough, Alicia A. Journal of the American Society of Nephrology. 33(9):1638-1640, September 2022.
A Comparison of US Medicare Expenditures for Hemodialysis and Peritoneal Dialysis
Authors: Jennifer M. Kaplan, Jingbo Niu, Vivian Ho, Wolfgang C. Winkelmayer, Kevin F. Erickson
Journal: Journal of the American Society of Nephrology (2022)

Significance Statement Observations that peritoneal dialysis (PD) may be an effective, lower-cost alternative to hemodialysis for treating ESKD led to US policies resulting in its increased use. The authors compared Medicare expenditures for patients who started in-center hemodialysis or PD between 2008 and 2015 and determined whether differences in expenditures across dialysis modalities persisted as more patients were placed on PD. Overall expenditures were 11% greater for hemodialysis versus PD, and this difference did not change over time as more patients initiated PD. Although estimated intravenous dialysis drug costs were higher for hemodialysis, this difference narrowed over time—possibly mitigating incentives for providers to start more patients on PD and explaining a recent plateauing of growth in initiating this dialysis modality in the United States. Background Observations that peritoneal dialysis (PD) may be an effective, lower-cost alternative to hemodialysis for the treatment of ESKD have led to policies encouraging PD and subsequent increases in its use in the United States. Methods In a retrospective cohort analysis of Medicare beneficiaries who started dialysis between 2008 and 2015, we ascertained average annual expenditures (for up to 3 years after initiation of dialysis) for patients ≥67 years receiving in-center hemodialysis or PD. We also determined whether differences in Medicare expenditures across dialysis modalities persisted as more patients were placed on PD. We used propensity scores to match 8305 patients initiating PD with 8305 similar patients initiating hemodialysis. Results Overall average expenditures were US$108,656 (2017) for hemodialysis and US$91,716 for PD (proportionate difference, 1.11; 95% confidence interval [CI], 1.09 to 1.13). This difference did not change over time ( P for time interaction term=0.14). Hemodialysis had higher estimated intravenous (iv) dialysis drug costs (1.69; 95% CI, 1.64 to 1.73), rehabilitation expenditures (1.35; 95% CI, 1.26 to 1.45), and other nondialysis expenditures (1.34; 95% CI, 1.30 to 1.37). Over time, initial differences in total dialysis expenditures disappeared and differences in iv dialysis drug utilization narrowed as nondialysis expenditures diverged. Estimated iv drug costs declined by US$2900 per patient-year in hemodialysis between 2008 and 2014 versus US$900 per patient-year in PD. Conclusions From the perspective of the Medicare program, savings associated with PD in patients ≥67 years have remained unchanged, despite rapid growth in the use of this dialysis modality. Total dialysis expenditures for the two modalities converged over time, whereas nondialysis expenditures diverged.
Optimizing Histology-Specific Clinical Trials in Soft-Tissue Sarcoma—Are We There Yet?
Authors: Christina L. Roland
Journal: JAMA Oncology (2022)

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Caution Regarding Assessment of Toxic Effects and Survival in Treatment De-escalation With Radiotherapy vs Transoral Surgery for Human Papillomavirus–Associated Oropharyngeal Cancer
Authors: Vinidh Paleri, Christian Simon, Philippe Gorphe
Journal: JAMA Oncology (2022)

To the Editor We commend Palma et al1 for presenting a randomized comparison of primary surgery vs radiation therapy for human papillomavirus–positive oropharyngeal cancer. However, we would caution against generalized applicability of ORATOR2 outcomes.
Interactions between spirometry and oscillometry in patients with moderate to severe asthma
Authors: Rory Chan, Brian Lipworth
Journal: European Respiratory Journal (2022)

<b>Small airways dysfunction defined by spirometry and oscillometry together confers worse outcomes in moderate to severe asthma. This emphasises the importance of combining spirometry and oscillometry to characterise the small airway asthma phenotype.</b>https://bit.ly/3CcaZ3e
Error in Byline
Journal: JAMA Network Open (2022)

Anna L. Funk, PhD, MSc; Nathan Kuppermann, MD, MPH; Todd A. Florin, MD, MSCE; Daniel J. Tancredi, PhD; Jianling Xie, MD, MPH; Kelly Kim, BSc; Yaron Finkelstein, MD; Mark I. Neuman, MD, MPH; Marina I. Salvadori, MD; Adriana Yock-Corrales, MD; Kristen A. Breslin, MD; Lilliam Ambroggio, PhD, MPH; Pradip P. Chaudhari, MD; Kelly R. Bergmann, DO, MS; Michael A. Gardiner, MD; Jasmine R. Nebhrajani, MD; Carmen Campos, MD; Fahd A. Ahmad, MD, MSCI; Laura F. Sartori, MD, MPH; Nidhya Navanandan, MD; Nirupama Kannikeswaran, MD; Kerry Caperell, MD, MS, MBA; Claudia R. Morris, MD; Santiago Mintegi, MD, PhD; Iker Gangoiti, MD; Vikram J. Sabhaney, MD; Amy C. Plint, MD; Terry P. Klassen, MD, MSc; Usha R. Avva, MD; Nipam P. Shah, MD, MBBS, MPH; Andrew C. Dixon, MD; Maren M. Lunoe, MD; Sarah M. Becker, MD; Alexander J. Rogers, MD; Viviana Pavlicich, MD; Stuart R. Dalziel, MBChB, PhD; Daniel C. Payne, PhD; Richard Malley, MD; Meredith L. Borland, MD; Andrea K. Morrison, MD, MS; Maala Bhatt, MD; Pedro B. Rino, MD; Isabel Beneyto Ferre, MD; Michelle Eckerle, MD; April J. Kam, MD; Shu-Ling Chong, MPH; Laura Palumbo, MD; Maria Y. Kwok, MD, MPH; Jonathan C. Cherry, MD; Naveen Poonai, MD; Muhammad Waseem, MD; Norma-Jean Simon, MPH; Stephen B. Freedman, MDCM, MSc; Pediatric Emergency Research Network–COVID-19 Study Team; Jessica Gómez-Vargas; Bethany Lerman; James Chamberlain; Adebola Owolabi; Camilla Schanche-Perret Gentil; Sofie Ringold; Jocy Perez; Heidi Vander Velden; Tyrus Crawford; Steven E Schultz; Kimberly Ross; Kathy Monroe; Karly Stillwell; Jillian Benedetti; Sharon O'Brien; Kyle Pimenta; Amia Andrade; Adam Isacoff; Kendra Sikes; Nina Gold; Kathleen Reichard; Maureen Nemetski; Pavani Avva; Rakesh Mistry; Shanon Young; Marlena Cook; Virginia Gómez Barrena ; Sandra Castejón Ramírez; María T García Castellanos; Emma Patterson; Anicka Samuel; Redjana Carciurmaru; Eleanor Fitzpatrick; Megan Bonisch; Bruce Wright; Mithra Sivakumar; Patricia Candelaria; Vincent Cervantes; Shaminy Manoranjithan; Nabeel Khan; Toni Harbour; Usha Sethuraman; Priya Spencer; Neha Gupta; Amira Kamboj; Gael Muanamputu; Guillermo Kohn Loncarica; Eugenia Hernández; Ana Dragovetzky; Angelats Carlos Miguel; Sylvia Torres; Joseph Zorc; Rebecca Haber; Ren Mee Hiong; Dianna Sri Dewi; Gary Joubert; Kamary Coriolano Dasilva; Julie Ochs; Alberto Arrighini; Camilla Dallavilla; Andrea Kachelmeyer; Daisy Marty Placencia
A Randomized Comparison of Nivolumab versus Nivolumab + Docetaxel for Previously Treated Advanced or Recurrent ICI-Naïve Non–Small Cell Lung Cancer: TORG1630
Authors: Yuri Taniguchi, Tsuneo Shimokawa, Yuichi Takiguchi, Toshihiro Misumi, Yukiko Nakamura, Yosuke Kawashima, Naoki Furuya, Yoshimasa Shiraishi, Toshiyuki Harada, Hisashi Tanaka, Satoru Miura, Ayumi Uchiyama, Yoshiro Nakahara, Takaaki Tokito, Katsuhiko Naoki, Akihiro Bessho, Yasuhiro Goto, Masahiro Seike, Hiroaki Okamoto
Journal: Clinical Cancer Research (2022)

Abstract Purpose: The addition of cytotoxic chemotherapy to immune-checkpoint inhibitor (ICI) may enhance antitumor effects. We conducted an open-label randomized phase II/III study to evaluate nivolumab + docetaxel combination therapy in comparison with nivolumab monotherapy for previously treated ICI-naïve non–small cell lung cancer (NSCLC). Patients and Methods: The primary endpoint of the phase III study was overall survival (OS), and the secondary endpoints included progression-free survival (PFS), overall response rate (ORR), and toxicity. As ICI and platinum-doublet combination chemotherapy was approved in the first-line setting during this study, patient accrual was discontinued. Results: One hundred twenty-eight patients (each arm, n = 64) were included in the full analysis set. The median OS in nivolumab (arm A) and nivolumab + docetaxel (arm B) was 14.7 months (95% CI, 11.4–18.7) and 23.1 months (95% CI, 16.7–NR), respectively. The HR for OS was 0.63 (90% CI, 0.42–0.95; P = 0.0310). The median PFS in arms A and arm B was 3.1 months (95% CI, 2.0–3.9) and 6.7 months (95% CI, 3.8–9.4), respectively. The HR for progression was 0.58 (95% CI, 0.39–0.88; P = 0.0095). The ORR was 14.0% (95% CI, 6.3–25.8) in arm A and 41.8% (95% CI, 28.7–55.9) in arm B. Hematotoxicity and gastrointestinal adverse events were more common in arm B than in arm A. Two treatment-related deaths were observed, including one patient in arm A who died of pneumonitis and one in arm B who died of myocarditis. Conclusions: Despite a slightly elevated toxicity, the addition of docetaxel to nivolumab has significantly prolonged the OS and PFS of patients with previously treated ICI-naïve NSCLC.
Handling Informative Premature Treatment or Study Discontinuation for Assessing Between-Group Differences in a Comparative Oncology Trial
Authors: Bo Huang, Ryan Sun, Brian Claggett, Lu Tian, Ethan B. Ludmir, Lee-Jen Wei
Journal: JAMA Oncology (2022)

This decision analytical model study examines premature treatment discontinuation in clinical trials for patients with advanced renal cell carcinoma.
Determinants and Effectiveness of Extending the Duration of Adjuvant Hormone Therapy beyond 5 Years in Patients with Breast Cancer
Authors: Erwei Zeng, Wei He, Arvid Sjölander, Jenny Bergqvist, Kamila Czene
Journal: Cancer Research (2022)

Abstract Clinical guidelines have recommended patients with high-risk breast cancer to extend adjuvant hormone therapy beyond 5 years. However, the prevalence, predictors, and outcomes of extended adjuvant hormone therapy in the real world remain unknown. By linking six Swedish health registries, we prospectively followed 13,168 patients with breast cancer (2005–2020) from their first prescription of tamoxifen or aromatase inhibitors and categorized them as extending or not extending adjuvant hormone therapy. Cox regression analysis was used to investigate whether extended therapy was associated with breast cancer outcomes. Among patients with breast cancer who were recommended to extend adjuvant hormone therapy by the national guidelines, the proportion of women who extended therapy increased 5 folds during the past 10 years, reaching 80.9% during 2018 to 2020. Patients were more likely to extend therapy after completing 5-year adjuvant hormone therapy if they were young [40 vs. ≥65 years: OR, 1.71; 95% confidence interval (CI), 1.13–2.58], had positive lymph nodes (OR, 2.25; 95% CI, 1.85–2.73), had high tumor grade (grade 3 vs. 1: OR, 1.79; 95% CI, 1.34–2.39), received chemotherapy (OR, 5.22; 95% CI, 4.19–6.50), had first-degree relatives who died from breast cancer (OR, 1.84; 95% CI, 1.21–2.81), or had a high income (OR, 1.23; 95% CI, 1.01–1.49). Extended use of adjuvant hormone therapy was statistically significantly associated with improved disease-free survival (HR, 0.72; 95 CI%, 0.55–0.95). This study provides real-world evidence showing the use and improved breast cancer outcomes of extended adjuvant hormone therapy beyond 5 years. Significance: The proportion of patients with breast cancer extending adjuvant hormone therapy beyond 5 years has increased dramatically in recent years, which is associated with improved patient outcomes.
Challenges Encountered in the Public Health Data Collection of COVID-19 Cases Among People Experiencing Homelessness
Authors: Sarah Axelrath
Journal: JAMA Network Open (2022)

Ashley A. Meehan, MPH; Isabel Thomas, MPH; Libby Horter, MPH; Megan Schoonveld, MPH; Andrea E. Carmichael, MPH; Mitra Kashani, MSc; Diana Valencia, MS; Emily Mosites, PhD
Validated allergen exposure chamber is plausible tool for the assessment of house dust mite‐triggered allergic rhinitis
Authors: Magdalena Zemelka‐Wiacek, Anna Kosowska, Ewa Winiarska, Ewa Sobanska, Marek Jutel
Journal: Allergy (2022)

Background Allergen exposure chamber (AEC) is a clinical facility that allows exposure to allergenic airborne particles in controlled environment. Although AECs offer stable levels of airborne allergens, the validation of symptoms and other endpoints induced by allergen challenge is key for their recommendation as a plausible tool for the assessment of patients, especially in clinical research. This study aimed to demonstrate the reproducibility of defined clinical endpoints after AEC house dust mite (HDM) challenge under optimal conditions in patients with allergic rhinitis (AR). Method HDM was distributed at different concentrations. The assessment was subjective by the patients: total nasal symptom score (TNSS), visual analog scale (VAS), and objective by the investigator: acoustic rhinometry, peak nasal inspiratory flow (PNIF), and nasal secretion weight. Safety was assessed clinically and by peak expiratory flow rate (PEFR) and forced expiratory volume in the first second (FEV1). Results Constant environment: temperature, humidity, and carbon dioxide (CO2) concentration were maintained during all challenges. The concentration of HDM on average remained stable within the targeted values: 1000, 3000, 5000, 7000 particles (p)/m3. Most symptoms were observed at concentrations 3000 p/m3 or higher. The symptoms severity and other endpoints results were reproducible. 5000 p/m3, and challenge duration of 120 min were found optimal. The procedure was safe with no lung function abnormalities due to challenge. Conclusion HDM challenge in ALL-MED AEC offers a safe and reliable method for inducing symptoms in AR patients for the use in controlled clinical studies including allergen immunotherapy.
Next generation sequencing reveals miR-431–3p/miR-1303 as immune-regulating microRNAs for active tuberculosis
Authors: Yung-Che Chen, Chang-Chun Hsiao, Chao-Chien Wu, Tung-Ying Chao, Sum-Yee Leung, Yu-Ping Chang, Chia-Cheng Tseng, Chiu-Ping Lee, Po-Yuan Hsu, Ting-Ya Wang, Po-Wen Wang, Ting-Wen Chen, Meng-Chih Lin
Journal: Journal of Infection (2022)
Hurdling over the blood–brain barrier with exosome technology
Authors: James Felker, Sameer Agnihotri
Journal: Neuro-Oncology (2022)

Journal Article Hurdling over the blood–brain barrier with exosome technology Get access James Felker, James Felker Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USADepartment of Pediatric Hematology/Oncology, UPMC Children’s Hospital of Pittsburgh, Pennsylvania, USA Corresponding Authors: James Felker, Children’s Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224, USA (james.felker@chp.edu) Search for other works by this author on: Oxford Academic PubMed Google Scholar Sameer Agnihotri Sameer Agnihotri Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USADepartment of Pediatric Hematology/Oncology, UPMC Children’s Hospital of Pittsburgh, Pennsylvania, USADepartment of Neurobiology, University of Pittsburgh, Pittsburgh, Pennsylvania, USADepartment of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USAJohn G. Rangos Sr. Research Center, Children’s Hospital of Pittsburgh, Pittsburgh, PA, USA Sameer Agnihotri, Children’s Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224, USA (sameer.agnihotri@pitt.edu). Search for other works by this author on: Oxford Academic PubMed Google Scholar Neuro-Oncology, Volume 24, Issue 11, November 2022, Pages 1884–1885, https://doi.org/10.1093/neuonc/noac214 Published: 31 August 2022 Article history Published: 31 August 2022 Corrected and typeset: 07 October 2022
<i>In vivo</i>functional characterization of EGFR variants identifies novel drivers of glioblastoma
Authors: Kwanha Yu, Kathleen Kong, Brittney Lozzi, Estefania Luna-Figueroa, Alexis Cervantes, Rachel Curry, Carrie A Mohila, Ganesh Rao, Ali Jalali, Gordon B Mills, Kenneth L Scott, Benjamin Deneen
Journal: Neuro-Oncology (2022)

Abstract Background Glioblastoma is the most common and aggressive primary brain tumor. Large-scale sequencing initiatives have cataloged its mutational landscape in hopes of elucidating mechanisms driving this deadly disease. However, a major bottleneck in harnessing this data for new therapies is deciphering “driver” and “passenger” events amongst the vast volume of information. Methods We utilized an autochthonous, in vivo screening approach to identify driver, EGFR variants. RNA-Seq identified unique molecular signatures of mouse gliomas across these variants, which only differ by a single amino acid change. In particular, we identified alterations to lipid metabolism, which we further validated through an unbiased lipidomics screen. Results Our screen identified A289I as the most potent EGFR variant, which has previously not been characterized. One of the mechanisms through which A289I promotes gliomagenesis is to alter cellular triacylglycerides through MTTP. Knockout of Mttp in mouse gliomas, reduces gliomagenesis in multiple models. Conclusions EGFR variants that differ by a single amino acid residue differentially promote gliomagenesis. Among the identified mechanism that drives glioma growth include lipid metabolism through MTTP. Understanding triacylglyceride accumulation may present a prospective therapeutic pathway for this deadly disease.